ESC: New Guidelines Are a Step Ahead of Regulators

Action Points

Explain to interested patients that new guidelines from the European Society of Cardiology for revascularization in heart attack patients recommend the use of an as-yet unapproved antiplatelet agent -- ticagrelor (Brilinta) -- as a recommended antithrombotic treatment.

Further explain that this appears to be the first time that guidelines have recommended a drug before its approval (and therefore prior to its availability) by either European or U.S. regulatory agencies.

STOCKHOLM -- The latest European Society of Cardiology guidelines for revascularization in myocardial infarction patients recommend the use of ticagrelor (Brilinta) -- an antiplatelet agent that has not yet been approved by any regulatory agency -- as a recommended antithrombotic treatment.

The new guidelines, released at the ESC meeting here, listed ticagrelor with a Class 1, Evidence Level B recommendation -- meaning that the recommendation is supported by evidence from a large clinical trial or from large nonrandomized studies, and there is general agreement that the treatment is "beneficial, useful, effective."

This is the same level of evidence given to clopidogrel (Plavix).

Prasugrel (Effient) received a Class IIa Evidence Level B recommendation, meaning that the "weight of the evidence or opinion is in favor of the usefulness or efficacy of the treatment."

Sidney C. Smith, Jr., MD, of the University of North Carolina at Chapel Hill, said the inclusion of ticagrelor struck him as reasonable since the PLATO trial, reported at the ESC a year ago, found that the drug, a non-thienopyridine ADP receptor blocker, was significantly superior to clopidogrel in reducing cardiovascular events -- including cardiovascular mortality.

Guidelines, Smith emphasized, are about "evidence, not politics."

The inclusion of ticagrelor in the new guidelines did, however, give pause to other cardiologists at the ESC meeting.

Ralph Brindis, MD, president of the American College of Cardiology, said that the inclusion of any unapproved drug in guidelines for clinicians was, to him, counterintuitive.

"I understand that one of the challenges [for guidelines committees] is to be as current as possible, but at the same time guidelines have to relevant to the practicing physician," Brindis said.

Including a drug that is not clinically available "does not make sense to the practicing clinician," he added.

Brindis is an interventional cardiologist and from that perspective, he said that he understands the anticipation surrounding the eventual approval of ticagrelor.

European regulators are expected to make a decision on ticagrelor in the next week or so, and the FDA is expected to issue its decision on the drug by mid-September -- so the ESC may be ahead of the curve by including ticagrelor at this point.

But regulators don't always make the expected decisions -- so there is no guarantee until an official announcement is made.

And even with the odds favoring approval for ticagrelor, including the drug in an official guideline still rankled some clinicians.

A. John Camm, MD, of St. George's University in London, who served on a joint ACC/AHA/ESC guidelines committee, said the inclusion of an unapproved drug was "inappropriate" -- adding that he would not recommend doing so.

But Clyde Yancy, MD, of Baylor College of Medicine in Houston told MedPage Today that it was "neither inappropriate nor unprecedented for regulatory agencies and clinical guideline committees to have separate and distinct thresholds."

He said that while the FDA "uses reasonably safe and effective" as its threshold for drug approval, guidelines committees focus on positive endpoints and "clinically important outcomes" when considering new treatments for inclusion in their guidelines.

At the same time, Yancy added that including a drug not yet approved by any regulatory agency did push the envelope, and Smith, who has chaired a number of ACC/AHA and National Institutes of Health guidelines committees said he could not recall an incidence in which a drug unapproved worldwide was included in any guideline.

Smith did, however, say that U.S. guideline groups have occasionally included recommendations about a drug that was already approved outside the U.S. but not approved by the FDA.

Despite repeated requests for comment by the ESC on the new guidelines, MedPage Today was unable to obtain a statement beyond these comments, issued in a press release:

"Our intention in writing these guidelines was to give patient-centered recommendations that lead to the most appropriate treatment regime for the different types of CAD. We also wanted to provide reference materials based on best practice but not conditioned by the skill and preferences of individual physicians. The major challenge faced by physicians is not how to treat the CAD patient, but which of the many treatment options to select." The comment was attributed to William Wijns, MD, PhD of the Cardiovascular Center in Moorselbaan, Belgium, who co-chaired the task force that wrote the new guidelines.

Hours after the ESC newsroom closed, the staff sent this response by e-mail:

"We have asked for interviews with the Chairs of this Guideline Review and as yet we have not been able to confirm availability in the schedule for an appropriate person to provide comment."

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